Applications of sharpless asymmetric dihydroxylation in the total synthesis of natural products

Kinetic detection of osmium(VI) ester intermediates during the OsO4‐mediated aqueous dihydroxylation of chloroethylenes

“…In the faster step, TCE, c ‐DCE, or t ‐DCE react with osmium(VIII) in a few seconds as evidenced by the small decrease of absorbance, which was detected in the entire spectral region above 280 nm (OsO 4 absorption). We attribute this absorbance change to the formation of the commonly assumed intermediate osmium(VI) ester complex . In the slower step, the reaction proceeds via the decomposition of the complexes in each investigated system, and the appropriate form of aqueous osmium(VI) is formed from the intermediate on a time scale of a few hours.…”

“…There seems to be quite general agreement on the mechanism of the cis dihydroxylation of carbon‐carbon double bonds by osmium tetroxide . The formation of the catalytically active osmium(VI) ester usually assumed to contain a tetrahedral d 2 metal center by the addition of OsO 4 to the double bond is a common feature of these processes.…”

“…Therefore, it is often imperative to use osmium as a catalyst in the process, which can be readily achieved by adding a less expensive stoichiometric oxidizing agent that is able to transform the product osmium(VI) back into osmium tetroxide. Hydrogen peroxide, tert ‐butyl‐hydroperoxide, N ‐methylmorpholine N ‐oxide, dioxygen, chlorate ion, hypochlorite ion, and periodate ion have all been reported to be suitable for this purpose under certain conditions . Despite the vastly different properties of these oxidants, it is a common aspect that they do not react with the substrate olefin directly, and their only role is to reproduce the initial form of the catalysts .…”

“…Hydrogen peroxide, tert ‐butyl‐hydroperoxide, N ‐methylmorpholine N ‐oxide, dioxygen, chlorate ion, hypochlorite ion, and periodate ion have all been reported to be suitable for this purpose under certain conditions . Despite the vastly different properties of these oxidants, it is a common aspect that they do not react with the substrate olefin directly, and their only role is to reproduce the initial form of the catalysts . Therefore, it is clear that the kinetics and the efficiency of a catalytic method are dominantly determined by the interaction of the oxidizable substrate with osmium tetroxide, and kinetic studies on this process in the absence of an extra oxidizing agent may provide insightful information on the mechanism and the potential application of the method.…”

“…However, these molecules might very well represent unreactive dead ends as far as the dihydroxylation process is concerned. The process can be carried out in an enantioselective way by adding coordinating chiral amines as coligands . These are understood to exert an influence on the process by coordinating to the osmium center directly.…”